It has recently been discovered that immunization of camelids (e.g., llamas) with non-camelid antigens (e.g., human antigens) results in production of conventional heterotetrameric antibodies with highly desirable properties. These conventional camelid antibodies have a strikingly high amino acid sequence and structural homology to human antibodies, and they bind to the non-camelid target antigen with high affinity. These antibodies also cover a wide diversity of epitopes on the non-camelid target antigen. Taken together, the properties of conventional camelid antibodies make them particularly attractive as therapeutics for the treatment of human disease.
It is often desirable to generate antibodies against precisely defined epitopes. Prior art techniques for raising antibodies against defined epitopes have generally involved the use of short peptides. These peptides can be used as immunogens to generate antibodies against only the target epitope or as selection tools to identify antibodies that bind the target epitope. This approach works well for linear epitopes but is often unsuccessful at generating or identifying antibodies that bind to epitopes that only exist in the native, 3-dimensional form of an antigen (i.e., conformational epitopes).
Accordingly, there is a need in the art for improved methods and compositions for the generation and selection of conventional camelid antibodies.